The p65 subunit of nuclear factor-κB is a molecular target for radiation sensitization of human squamous carcinoma cells

The transcription factor nuclear factor-κB (NF-κB) is activated in response to various stimuli including ionizing radiation. Disruption of NF-κB activation by mutant forms of the NF-κB inhibitor IκB-α or by proteasome inhibitors enhances both sensitivity to radiation and radiation-induced apoptosis. Human squamous carcinoma SCC-35 cells stably expressing a fragment (residues 1 to 84) of human p65 have been shown to exhibit down-regulation of both endogenous p65 mRNA and its protein. The mutant protein also inhibited radiation-induced NF-κB activation by preventing the proteolysis of IκB-α. This resulted in enhancement of cellular radiosensitivity and radiation-induced apoptosis. The NH2-terminal region of p65 is thus a potential molecular target for disruption of NF-κB activation and sensitization of tumors to radiotherapy.